We have investigated the presence of dominant transforming genes in human tumors by DNA-mediated gene transfer experiments. High molecular weight DNAs from carcinomas and sarcomas were tested in transfection assays. Nine of these DNAs, including those isolated from pancreatic and colon carcinomas and from an embryonic rhabdomyosarcoma, induced morphologic transformation in recipient mouse NIH/3T3 fibroblasts. Our goal is to determine whether these transforming genes are etiologically involved in human neoplasias.